Pain sensitivity in Parkinson's disease: Systematic review and meta-analysis

Introduction: Pain is a common and disabling non-motor symptom of Idiopathic Parkinson's disease (PD) but its underlying pathophysiological mechanisms are not well understood. There is evidence to suggest that altered pain sensitivity may contribute to the experience of pain in PD patients, but clinical studies investigating this have yielded inconsistent results. Objectives: To examine whether pain thresholds are altered in PD patients compared to normal healthy controls (HC), via the use of systematic review and meta-analysis. Data sources: A systematic search of the MEDLINE and EMBASE library from 1966 to April 2015. Study selection: Studies that compared pain thresholds in PD patients versus HC were included in the systematic review. Additionally, data comparing PD patients off dopaminergic medications (PDMoff) to HC off medications (HCMoff) were pooled for meta-analysis by pain modality. Main outcomes: Heat pain threshold, cold pain threshold, electrical pain threshold, nociceptive withdrawal reflex threshold, pressure pain threshold, and pain ratings. Results: 22 studies were reviewed, comprising of 616 PD and 451 MC. In the comparison of PDMoff versus HCMoff, a large majority of trials (15/19) found reduced pain thresholds (increased pain sensitivity) in PD patients. Meta-analysis of these trials revealed significantly reduced pain thresholds, of moderate to large effect size, in PD patients across all pain modalities. Results were much more heterogenous when PD patients on medications were compared with HC off medications, with most trials reporting no significant difference in pain thresholds between groups. No significant differences were found in pain thresholds for trials that compared PD patients on medications and HC on medications. Conclusion: PD patients are more sensitive to noxious stimuli compared to HC when tested in the off medication state. This increase in pain sensitivity is observed across all modalities, but is not as apparent when PD patients are administered Levodopa, suggesting that dopamine deficient states may contribute to hyperalgesia. However, it remains to be seen whether or not increased pain sensitivity translates clinically into increased prevalence of pain. Similarly, it is unclear if dopaminergic medications influence pain sensitivity. Performing a meta-analysis on studies comparing pain thresholds in PD patients with and without pain, and on and off dopaminergic medications, may draw more definitive conclusions in this regard. (C) 2017 Published by Elsevier Ltd.